Thymidine (Tdr) selectively inhibits the groth of Tdr-sensitive EL4 tumor cells in syngeneic C57BL/6 mice. The lives of the mice are prolonged for a period equivalent to that achieved by a 1000-fold reduction in tumor cells. We will determine whether Tdr actually acts as a cytotoxic agent to decrease the number of viable tumor cells, or whether it acts as a cytostatic agent to slow the replication of the cells. We will do this by injecting mice with 200 Tdr-sensitive EL4cells, treating them with Tdr, and then comparing the number of mice that survive with the number of mice that are expected to survive if Tdr acted as a cytotoxic agent. EL4 cells build up very large pools of dTTP when grown in Tdr. We will determine whether the cells are unusually sensitive to Tdr because they can not catabolize Tdr and thus can not drain their pools of excess dTTP. We will also determine whether EL4 cells that mutate to Tdr-resistance regain their Tdr-catabolizing activity or whether they have altered the amounts or the structure of their ribonucleotide reductase so that they may continue to make adequate amounts of dCTP for growth in the presence of excess dTTP. These determinations will be made by comparing Tdr-catabolizing activity, and ribonucleotide reductase activity in extracts of Tdr-sensitive EL4 cells, of Tdr-resistant EL4 cells, and of normal T lymphocytes.